Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion

Abstract

It is well known that the hypothalamo-pituitary-adrenal (HPA) axis is altered by early environmental experiences, particularly in the perinatal period. This may be one mechanism by which the environment changes the physiology of the animal such that individual differences in adult adaptative capabilities, such as behavioral reactivity and memory performance, are observable. To determine the origin of these behavioral individual differences, we have investigated whether the long-term influence of prenatal and postnatal experiences on emotional and cognitive behaviors in adult rats are correlated with changes in HPA activity. To this end, prenatal stress of rat dams during the last week of gestation and postnatal daily handling of rat pups during the first 3 weeks of life were used as two environmental manipulations. The behavioral reactivity of the adult offspring in response to novelty was evaluated using four different parameters: the number of visits to different arms in a Y-maze, the distance covered in an open field, the time spent in the corners of the open field, and the time spent in the open arms of an elevated plus-maze. Cognitive performance was assessed using a water maze and a two-trial memory test. Adult prenatally stressed rats showed high anxiety-like behavior, expressed as an escape behavior to novelty correlated with high secretion of corticosterone in response to stress, whereas adult handled rats exhibited low anxiety-like behavior, expressed as high exploratory behavior correlated with low secretion of corticosterone in response to stress. On the other hand, neither prenatal stress nor handling changed spatial learning or memory performance. Taken together, these results suggest that individual differences in adult emotional status may be governed by early environmental factors; however, perinatal experiences are not effective in influencing adult memory capacity.

Fig. 1.

Plasma corticosterone secretion (μg/100 ml) in basal condition (time, 0 min) and in response to a 30 min restraint stress (time, 30 and 120 min) (mean ± SEM). The basal (T0) and peak stress (T30) levels were similar for the three groups; however, 2 hr after stress, animals of the prenatal stress (PS) group showed a prolonged stress-induced corticosterone secretion, whereas this secretion was reduced in the handling (H) group compared with control (C) group. PS versus C, **p < 0.01; PS versus H, +++p < 0.001; H versus C, *p < 0.02.

Fig. 2.

Number of visits (mean ± SEM) to separate arms of the Y-maze over the two 5 min halves of the 10 min test. Although animals of the PS group exhibited a higher locomotor activity than animals of C and H groups over the first 5 min, the scores were identical in the last 5 min. PS versus C, ***p < 0.001; PS versus H, +++p < 0.001.

Fig. 3.

Distance covered (m) (A) and time spent in corners (sec) (B) in the open field in the three 5 min intervals of the 15 min test (mean ± SEM). The PS group covered more distance than did the other two groups over the first 5 min, indicating a high initial activity. PS versus C, **p < 0.01; PS versus H, +++p< 0.001. Differences were observed for the time spent in corners in the 5–10 and 10–15 min periods. Postnatally handled rats exhibited a lower score than did control and prenatally stressed rats, indicating that they searched less for a place of refuge. 5–10 min period: H versus C, **p < 0.01; H versus PS, ++p < 0.01. 10–15 min period: H versus C, *p < 0.02; H versus PS, +++p< 0.001.

Fig. 4.

Percentage of time spent in open arms (open/open + closed) measured in the elevated plus-maze over the 10 min test (mean ± SEM). Prenatally stressed rats had a lower score than that of control and handled rats, whereas the score of the handled rats was higher than the one of control rats, indicating that prenatally stressed rats took refuge more than the other two groups. PS versus C, **p < 0.01; PS versus H, +++p< 0.001; H versus C, **p < 0.01.

Fig. 5.

PCA of behavioral variables. Two factors were extracted. F1 is represented by the horizontal axis and F2 by the vertical axis. F1 accounts for 43.6% of the total variance and F2, 30.8%. The locations of the variables in this analysis are represented by a circle and correspond to the following parameters:Y-maze visits = number of visits in the Y-maze during the first 5 min; Open-field distance = distance covered in the open field during the first 5 min;Open-field corner = time spent in corners in the open field during the 10–15 min period; Plus-maze open arm = time spent (%) in open arms of the elevated plus-maze during the 10 min of the test. Factor 1 (F1) has been defined as exploration and factor 2 (F2) as escape behavior.

Fig. 6.

Performance scores in the learning phase and reversal phase of the water maze. The parameters measured were the distance (A) and latency (B) to escape onto the hidden platform. The performance improved for all groups, over the 7 d of learning and the 3 d of reversal, for both the distance and latency measures. Prenatal stress (PS), control (C), and handling (H) groups did not differ in cognitive capability.

Fig. 7.

Performance scores in the two-trial memory task in the Y-maze at four intertrial intervals (ITI). The parameters measured were the number of visits to the novel arm (%) (A) and the time spent in the novel arm (%) (B). PS, C, and H groups performed identically for the two parameters in each ITI session. The dotted linerepresents the chance level (33%) of visits in the three arms.